Role Of Lipids In Colon, Breast, And Other Cancers

动物和人类流行病学研究支持花生四烯酸（AA）和亚油酸（LA）代谢的重要性，这些研究表明阿司匹林和其他NSAID可抑制考克斯活性，降低结肠癌的发病率和死亡率，并减少家族性息肉病患者的息肉。对啮齿动物的实验研究表明，非甾体类抗炎药可减少致癌物诱发的结肠肿瘤的大小和数量。前列腺素和其他脂质在结肠癌和其他癌症的发展和进展中起着重要作用，但其机制尚不清楚。我们最近发现，在转基因小鼠模型中，考克斯-2在胚胎发育过程中的过表达导致许多生理缺陷，最终导致胎儿死亡。最引人注目的影响是骨骼发育引起的诱导细胞凋亡的转基因胚胎的硬组织。这是在其他组织中未观察到的特异性反应。此外，在转基因胚胎中观察到p53蛋白的巩膜组织积聚，这表明考克斯-2可能通过上调p53诱导细胞凋亡。在胚胎发育过程中异常的考克斯-2信号传导是致畸的，并提示考克斯-2可能与病因不明的胎儿畸形相关。

The importance of arachidonic acid (AA) and linoleic acid (LA) metabolism is supported by animal and human epidemiology studies that indicate that aspirin and other NSAIDs that inhibit COX activity, reduce the incidence and mortality of colon cancer and reduce polyps in patients with familial polyposis. Experimental studies with rodents indicate that NSAIDs reduce both the size and number of colon tumors induced by carcinogens. Prostaglandins and other lipids play a major role in the development and progression of colon and other cancers but the mechanism is not clear. We have recently discovered that the overexpression of COX-2 in a transgenic mouse model during embryonic development results in a number of physiological defects, ultimately resulting in the death of the fetus. The most dramatic effects were on skeletal development caused by the induction of apoptosis in the sclerotome of the transgenic embryos. This was a specific response not observed in other tissues. In addition, the sclerotomal accumulation of p53 protein is observed in transgenic embryos, suggesting that COX-2 may induce apoptosis via the up-regulation of p53. The aberrant COX-2 signaling during embryonic development is teratogenic and suggests a possible association of COX-2 with fetal malformations of unknown etiology.